Ciclosporin (Cyclosporin) Intravenous Infusion for Adults

Who can administer

May be administered by registered competent doctor or nurse/midwife

Important information

• See monitoring requirements
• There are numerous important interactions - check BNF
• Must have access to facilities for managing hypersensitivity reactions including anaphylaxis- due to polyethoxylated castor oil
• Dose adjustments needed in renal impairment- specialist review required
• Low adsorption giving set and bag required
• If switching from oral to iv consult specialist team e.g. nephrology as dose modification and risk assessment required

Available preparations

Sandimmun 50mg per 1ml ampoule

Reconstitution

Already in solution

Draw up using a 5 micron filter needle

Dilute further prior to administration

Infusion fluids

Sodium chloride 0.9% or Glucose 5% (Braun ecoflac or Macroflex containers - low adsorption)

Methods of intravenous administration

IMPORTANT for all intravenous routes of administration:

• Incompatible with PVC - a low adsorption infusion bottle (Braun ecoflac, or Baxter Viaflo) and a low adsorption giving set (e.g. Baxter VMC9606, or Braun 8700110SP) must be used
• The low adsorption set may be obtained from pharmacy
• Alternatively, a syringe pump and a low adsorption administration set (e.g Vygon Lectro-spiral 1155.80 or Braun Original Perfusor - Leitung PE 8723060 ) can be used

Intermittent intravenous infusion (administer using an electronically controlled infusion device)

• Used in early post-transplantation stage, or if oral therapy not possible e.g. post-surgery, or during episodes of GI disturbances
• Add required dose to a suitable volume of infusion fluid and administer over 2 to 6 hours (this infusion time may be used for any dose)
• The dose must be diluted between 1:20 to 1:100 to give a final concentration of between 0.5 and 2.5mg/ml
• Example (using 50mg/1ml amps)
• 50mg (1ml) in 20 to 100ml of infusion fluid
• 100mg (2ml) in 40 to 200ml of infusion fluid
• 200mg (4ml) in 80 to 400ml infusion fluid
• Mix well after addition to infusion fluid
• The residual volume in the infusion line must be flushed through at the same rate to avoid significant underdosing

Continuous intravenous infusion (administer using an electronically controlled infusion device)

• Used for the treatment of Ulcerative colitis (unlicensed)
• A continuous 24 hour infusion is used (ref 1,2)
• Mix well after addition to infusion fluid

Dose in adults

Temporary conversion of oral to intravenous therapy

• The total daily intravenous dose is approximately one-third of the total daily oral dose
• Oral dosing should commence as soon as possible
• Consider specialist advice- consult transplant team

Transplantation and autoimmune disorders

• Specialist advice should be taken before using this product
• For transplantation, various dosing regimens are used in specialist centres and higher doses are used initially
• Use IV route only if oral dosing not possible or if absorption is unreliable e.g. due to GI disturbance
• Dose reduction is recommended if a sustained rise in serum creatinine occurs - consult with transplant team before making any dose adjustments

Ulcerative colitis

• This is an unlicensed indication.
• Specialist advice should be taken before prescribing this product.
• A dose of 2mg/kg over twenty-four hours has been used (1,2)

Renal impairment

• Seek specialist advice
• Rises in serum creatinine while on ciclosporin will require specialist review

Hepatic impairment

• Dose adjustment may be required in hepatic impairment - seek specialist advice

Monitoring

• Observe patient continuously for at least 30 minutes after starting the infusion and at frequent intervals thereafter
• Monitor whole blood trough level routinely in transplant patients, and following co-administration of interacting drugs, otherwise only if non-compliance suspected
• Need to state dose regimen, time and date of both last dose and of sample time on blood specimen
• There are very few guidelines on the desired blood levels - this is because the required range can depend on the indication, time post- transplant (if being used for this indication), and on the assay methods used to test samples. Seek specialist advice.
• Markedly nephrotoxic, check baseline serum creatinine then monitor frequently
• Need to distinguish between rejection and ciclosporin induced nephrotoxicity in transplant patients if serum creatinine rises.
• During the concomitant use of a drug that may exhibit nephrotoxic synergy, closely monitor renal function
• Monitor liver function, blood pressure, serum potassium, magnesium and lipids

Further information

• Must be given in a non-PVC bag (e.g. Ecoflac or Macroflex) and giving-set to prevent leaching of toxic DEHP from PVC
• Check for numerous interactions, including St. John's Wort - specialist advice required if interacting drug added
• Vaccinations may be less effective; avoid live attenuated vaccines

Storage

Store below 25⁰C

References

SPC March 2021

1: Long term results of low-dose intravenous ciclosporin for acute severe ulcerative colitis. Rayner C.K et al Aliment Pharmacol Ther 2003; 18: 303-308

2: Randomised double blind comparison of 4mg/kg vs 2mg/kg Intravenous ciclosporin in severe ulcerative colitis Assche et al, Gastroenterology 2003;125:1025-1031

Therapeutic classification

Immunosuppressant